The long-term goal of the proposed research is to understand the mechanisms by which glia cells help to regulate the extracellular environment in the brain. The premise underlying this work is that high-affinity membrane transport systems in glia are important contributors to the regulation of the extracellular environment and that a more complete understanding of the mechanism of these systems is needed to evaluate their contributions. All high-affinity systems studied so far are Na(plus)-dependent. The energetics of sodium-dependent systems is thought to depend on Na(plus) and K(plus) ion gradients across the membrane, the membrane potential, transport stoichiometry, and the electrical charge on the substrate. We plan to investigate the transport of three neurochemically important compounds, taurine, glutamate, and choline, by rat glioma cells maintained in cell culture. These studies are designed to determine whether the ion gradients and membrane potential do, in fact, provide the energy for the transport of these three compounds and the extent to which changes in membrane potential can influence the rate and direction of transport.